Olfaction is a critical chemosensory modality used by animals to gather information concerning the external environment. The olfactory system mediates behaviors such as food localization, mate selection, predator avoidance and parent-offspring interactions. Initially, it was believed that the main olfactory system (MOS) conveyed information regarding 'general' odorants while the accessory olfactory system (AOS) responded to 'socially related' ones (semiochemicals). However, recent discoveries suggest that this classification is no longer appropriate. In most terrestrial vertebrates including mice, a portion of the MOS works in parallel with the AOS to convey odorant information regarding semiochemicals to the medial amygdala (MeA). The MeA is a collection of nuclei located in the medial temporal lobe previously shown to be essential in many socially relevant behaviors. The MeA has extensive interconnections with the hypothalamus and therefore exerts significant influence upon the hormonal state of the animal. Knowledge of the mechanisms that both MOS and AOS pathways employ to process/transmit semiochemical odorants is key to understanding how these streams of information are integrated by higher brain structures (i.e. MeA) which drive the resulting behavior. Recent investigations suggest that semiochemical information is detected by those ciliated OSNs that express the transient receptor potential channel (TrpM5) and which project to the ventral MOB. A subpopulation of mitral cells in the ventral main olfactory bulb (MOB) sends axons to the MeA. The current project is aimed at characterizing TrpM5-expressing receptor neurons as the initial components of a neural pathway projecting from the MOS to the MeA in male mice. The proposed project will utilize molecular and biochemical techniques to test whether TrpM5-expressing OSNs transmit information regarding semiochemicals to the subset of mitral cells in the MOB that project to the MeA. The functional contribution of TrpM5 to this pathway will also be measured. The Specific Aims are the following: 1) to test whether those Mitral cells of the MOB that project to the medial amygdala, preferentially receive input from TrpM5-positive glomeruli, and 2) to test whether TrpM5 is both sufficient and necessary for functionality of the MOS neural pathway involved in transmission of semiochemical odorant information to the MeA. The results obtained from the proposed experiments will aid in understanding how the MOS processes socially-related odors. These findings will be important in understanding how species (e.g. humans) that lack a functional AOS can still detect and respond to social odor cues. PUBLIC HEALTH RELEVANCE: The proposed project will elucidate how the main olfactory system processes socially-related odor signals important for mate selection and identification of individuals.